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Dr Mattia Frontini

Dr Mattia Frontini

BHF Senior Basic Science Research Fellow


Research themes

Functional Genomics:

Research Interests

Dr Mattia Frontini has recently been awarded his first BHF Senior Research Fellowship (2019-2024) and has been interviewed for our 'Spotlight on...' article series - read more about his research here.

I am currently a Senior Research Associate in Prof Willem Ouwehand’s group, where I lead a team responsible for the isolation of healthy blood cell samples for the BluePrint consortium.

My 2-year Career Development Fellowship by the BHF Cambridge Centre of Excellence has focused on the interplay between chronic inflammation and myeloid cells production.

This is an important field of study because diseases that share chronic inflammation often present an increased risk of cardiovascular diseases and exposure to chronic inflammation trigger an increased production of white blood cells with prothrombotic phenotype.

Keywords

BLUEPRINT ; epigenetics ; epigenomics ; blood cells ; haematopoiesis

Key Publications

Full list of publications can be found here.

Histone Acetyltransferase KAT2A Stabilizes Pluripotency with Control of Transcriptional Heterogeneity. Moris N, Edri S, Seyres D, Kulkarni R, Domingues AF, Balayo T, Frontini M, Pina C. Stem Cells. 2018 Oct 1.

Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation to Mature Blood Neutrophils. Grassi L, Pourfarzad F, Ullrich S, Merkel A, Were F, Carrillo-de-Santa-Pau E, Yi G, Hiemstra IH, Tool ATJ, Mul E, Perner J, Janssen-Megens E, Berentsen K, Kerstens H, Habibi E, Gut M, Yaspo ML, Linser M, Lowy E, Datta A, Clarke L, Flicek P, Vingron M, Roos D, van den Berg TK, Heath S, Rico D, Frontini M, Kostadima M, Gut I, Valencia A, Ouwehand WH, Stunnenberg HG, Martens JHA, Kuijpers TW. Cell Rep. 2018 Sep 4;24(10):2784-2794.

Chromosome contacts in activated T cells identify autoimmune disease candidate genes. Burren OS, Rubio García A, Javierre BM, Rainbow DB, Cairns J, Cooper NJ, Lambourne JJ, Schofield E, Castro Dopico X, Ferreira RC, Coulson R, Burden F, Rowlston SP, Downes K, Wingett SW, Frontini M, Ouwehand WH, Fraser P, Spivakov M, Todd JA, Wicker LS, Cutler AJ, Wallace C. Genome Biol. 2017 Sep 4;18(1):165.

Platelet function is modified by common sequence variation in megakaryocyte super enhancers. Petersen R, Lambourne JJ, Javierre BM, Grassi L, Kreuzhuber R, Ruklisa D, Rosa IM, Tomé AR, Elding H, van Geffen JP, Jiang T, Farrow S, Cairns J, Al-Subaie AM, Ashford S, Attwood A, Batista J, Bouman H, Burden F, Choudry FA, Clarke L, Flicek P, Garner SF, Haimel M, Kempster C, Ladopoulos V, Lenaerts AS, Materek PM, McKinney H, Meacham S, Mead D, Nagy M, Penkett CJ, Rendon A, Seyres D, Sun B, Tuna S, van der Weide ME, Wingett SW, Martens JH, Stegle O, Richardson S, Vallier L, Roberts DJ, Freson K, Wernisch L, Stunnenberg HG, Danesh J, Fraser P, Soranzo N, Butterworth AS, Heemskerk JW, Turro E, Spivakov M, Ouwehand WH, Astle WJ, Downes K, Kostadima M, Frontini M. Nat Commun. 2017 Jul 13;8:16058.

SNP in human ARHGEF3 promoter is associated with DNase hypersensitivity, transcript level and platelet function, and Arhgef3 KO mice have increased mean platelet volume. Zou S, Teixeira AM, Kostadima M, Astle WJ, Radhakrishnan A, Simon LM, Truman L, Fang JS, Hwa J, Zhang PX, van der Harst P, Bray PF, Ouwehand WH, Frontini M, Krause DS. PLoS One. 2017 May 23;12(5):e0178095.

Megakaryocytes in Myeloproliferative Neoplasms Have Unique Somatic Mutations. Guo BB, Allcock RJ, Mirzai B, Malherbe JA, Choudry FA, Frontini M, Chuah H, Liang J, Kavanagh SE, Howman R, Ouwehand WH, Fuller KA, Erber WN. Am J Pathol. 2017 Jul;187(7):1512-1522.

Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging. Tarkin JM, Joshi FR, Evans NR, Chowdhury MM, Figg NL, Shah AV, Starks LT, Martin-Garrido A, Manavaki R, Yu E, Kuc RE, Grassi L, Kreuzhuber R, Kostadima MA, Frontini M, Kirkpatrick PJ, Coughlin PA, Gopalan D, Fryer TD, Buscombe JR, Groves AM, Ouwehand WH, Bennett MR, Warburton EA, Davenport AP, Rudd JH. J Am Coll Cardiol. 2017 Apr 11;69(14):1774-1791.

CSB ablation induced apoptosis is mediated by increased endoplasmic reticulum stress response. Caputo M, Balzerano A, Arisi I, D'Onofrio M, Brandi R, Bongiorni S, Brancorsini S, Frontini M, Proietti-De-Santis L. PLoS One. 2017 Mar 2;12(3):e0172399.

Potency of Human Cardiosphere-Derived Cells from Patients with Ischemic Heart Disease Is Associated with Robust Vascular Supportive Ability. Harvey E, Zhang H, Sepúlveda P, Garcia SP, Sweeney D, Choudry FA, Castellano D, Thomas GN, Kattach H, Petersen R, Blake DJ, Taggart DP, Frontini M, Watt SM, Martin-Rendon E. Stem Cells Transl Med. 2017 May;6(5):1399-1411.

Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types. Ecker S, Chen L, Pancaldi V, Bagger FO, Fernández JM, Carrillo de Santa Pau E, Juan D, Mann AL, Watt S, Casale FP, Sidiropoulos N, Rapin N, Merkel A; BLUEPRINT Consortium, Stunnenberg HG, Stegle O, Frontini M, Downes K, Pastinen T, Kuijpers TW, Rico D, Valencia A, Beck S, Soranzo N, Paul DS. Genome Biol. 2017 Jan 26;18(1):18.

Increased DNA methylation variability in type 1 diabetes across three immune effector cell types. Paul DS, Teschendorff AE, Dang MA, Lowe R, Hawa MI, Ecker S, Beyan H, Cunningham S, Fouts AR, Ramelius A, Burden F, Farrow S, Rowlston S, Rehnstrom K, Frontini M, Downes K, Busche S, Cheung WA, Ge B, Simon MM, Bujold D, Kwan T, Bourque G, Datta A, Lowy E, Clarke L, Flicek P, Libertini E, Heath S, Gut M, Gut IG, Ouwehand WH, Pastinen T, Soranzo N, Hofer SE, Karges B, Meissner T, Boehm BO, Cilio C, Elding Larsson H, Lernmark Å, Steck AK, Rakyan VK, Beck S, Leslie RD. Nat Commun. 2016 Nov 29;7:13555.

DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation. Farlik M, Halbritter F, Müller F, Choudry FA, Ebert P, Klughammer J, Farrow S, Santoro A, Ciaurro V, Mathur A, Uppal R, Stunnenberg HG, Ouwehand WH, Laurenti E, Lengauer T, Frontini M, Bock C. Cell Stem Cell. 2016 Nov 16. pii: S1934-5909(16)30360-5.

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease. Astle WJ, Elding H, Jiang T, Allen D, Ruklisa D, Mann AL, Mead D, Bouman H, Riveros-Mckay F, Kostadima MA, Lambourne JJ, Sivapalaratnam S, Downes K, Kundu K, Bomba L, Berentsen K, Bradley JR, Daugherty LC, Delaneau O, Freson K, Garner SF, Grassi L, Guerrero J, Haimel M, Janssen-Megens EM, Kaan A, Kamat M, Kim B, Mandoli A, Marchini J, Martens JH, Meacham S, Megy K, O'Connell J, Petersen R, Sharifi N, Sheard SM, Staley JR, Tuna S, van der Ent M, Walter K, Wang SY, Wheeler E, Wilder SP, Iotchkova V, Moore C, Sambrook J, Stunnenberg HG, Di Angelantonio E, Kaptoge S, Kuijpers TW, Carrillo-de-Santa-Pau E, Juan D, Rico D, Valencia A, Chen L, Ge B, Vasquez L, Kwan T, Garrido-Martín D, Watt S, Yang Y, Guigo R, Beck S, Paul DS, Pastinen T, Bujold D, Bourque G, Frontini M, Danesh J, Roberts DJ, Ouwehand WH, Butterworth AS, Soranzo N. Cell. 2016 Nov 17;167(5):1415-1429.e19.

Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells. Chen L, Ge B, Casale FP, Vasquez L, Kwan T, Garrido-Martín D, Watt S, Yan Y, Kundu K, Ecker S, Datta A, Richardson D, Burden F, Mead D, Mann AL, Fernandez JM, Rowlston S, Wilder SP, Farrow S, Shao X, Lambourne JJ, Redensek A, Albers CA, Amstislavskiy V, Ashford S, Berentsen K, Bomba L, Bourque G, Bujold D, Busche S, Caron M, Chen SH, Cheung W, Delaneau O, Dermitzakis ET, Elding H, Colgiu I, Bagger FO, Flicek P, Habibi E, Iotchkova V, Janssen-Megens E, Kim B, Lehrach H, Lowy E, Mandoli A, Matarese F, Maurano MT, Morris JA, Pancaldi V, Pourfarzad F, Rehnstrom K, Rendon A, Risch T, Sharifi N, Simon MM, Sultan M, Valencia A, Walter K, Wang SY, Frontini M, Antonarakis SE, Clarke L, Yaspo ML, Beck S, Guigo R, Rico D, Martens JH, Ouwehand WH, Kuijpers TW, Paul DS, Stunnenberg HG, Stegle O, Downes K, Pastinen T, Soranzo N. Cell. 2016 Nov 17;167(5):1398-1414.e24.

Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters. Javierre BM, Burren OS, Wilder SP, Kreuzhuber R, Hill SM, Sewitz S, Cairns J, Wingett SW, Várnai C, Thiecke MJ, Burden F, Farrow S, Cutler AJ, Rehnström K, Downes K, Grassi L, Kostadima M, Freire-Pritchett P, Wang F; BLUEPRINT Consortium., Stunnenberg HG, Todd JA, Zerbino DR, Stegle O, Ouwehand WH, Frontini M, Wallace C, Spivakov M, Fraser P. Cell. 2016 Nov 17;167(5):1369-1384.e19.

Saturation analysis for whole-genome bisulfite sequencing data. Libertini E, Heath SC, Hamoudi RA, Gut M, Ziller MJ, Herrero J, Czyz A, Ruotti V, Stunnenberg HG, Frontini M, Ouwehand WH, Meissner A, Gut IG, Beck S. Nat Biotechnol. 2016 Jun 27.

Information recovery from low coverage whole-genome bisulfite sequencing. Libertini E, Heath SC, Hamoudi RA, Gut M, Ziller MJ, Czyz A, Ruotti V, Stunnenberg HG, Frontini M, Ouwehand WH, Meissner A, Gut IG, Beck S. Nat Commun. 2016 Jun 27;7:11306.

Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Saeed S, Quintin J, Kerstens HH, Rao NA, Aghajanirefah A, Matarese F, Cheng SC, Ratter J, Berentsen K, van der Ent MA, Sharifi N, Janssen-Megens EM, Ter Huurne M, Mandoli A, van Schaik T, Ng A, Burden F, Downes K, Frontini M, Kumar V, Giamarellos-Bourboulis EJ, Ouwehand WH, van der Meer JW, Joosten LA, Wijmenga C, Martens JH, Xavier RJ, Logie C, Netea MG, Stunnenberg HG. Science. 2014 Sep 26;345(6204):1251086.

Transcriptional diversity during lineage commitment of human blood progenitors. Chen L, Kostadima M, Martens JH, Canu G, Garcia SP, Turro E, Downes K, Macaulay IC, Bielczyk-Maczynska E, Coe S, Farrow S, Poudel P, Burden F, Jansen SB, Astle WJ, Attwood A, Bariana T, de Bono B, Breschi A, Chambers JC; BRIDGE Consortium, Choudry FA, Clarke L, Coupland P, van der Ent M, Erber WN, Jansen JH, Favier R, Fenech ME, Foad N, Freson K, van Geet C, Gomez K, Guigo R, Hampshire D, Kelly AM, Kerstens HH, Kooner JS, Laffan M, Lentaigne C, Labalette C, Martin T, Meacham S, Mumford A, Nürnberg S, Palumbo E, van der Reijden BA, Richardson D, Sammut SJ, Slodkowicz G, Tamuri AU, Vasquez L, Voss K, Watt S, Westbury S, Flicek P, Loos R, Goldman N, Bertone P, Read RJ, Richardson S, Cvejic A, Soranzo N, Ouwehand WH, Stunnenberg HG, Frontini M, Rendon A. Science. 2014 Sep 26;345(6204):1251033.

The cockayne syndrome B protein is essential for neuronal differentiation and neuritogenesis. Ciaffardini F, Nicolai S, Caputo M, Canu G, Paccosi E, Costantino M, Frontini M, Balajee AS, Proietti-De-Santis L. Cell Death Dis. 2014 May 29;5:e1268.

SMIM1 underlies the Vel blood group and influences red blood cell traits. Cvejic A, Haer-Wigman L, Stephens JC, Kostadima M, Smethurst PA, Frontini M, van den Akker E, Bertone P, Bielczyk-Maczyńska E, Farrow S, Fehrmann RS, Gray A, de Haas M, Haver VG, Jordan G, Karjalainen J, Kerstens HH, Kiddle G, Lloyd-Jones H, Needs M, Poole J, Soussan AA, Rendon A, Rieneck K, Sambrook JG, Schepers H, Silljé HH, Sipos B, Swinkels D, Tamuri AU, Verweij N, Watkins NA, Westra HJ, Stemple D, Franke L, Soranzo N, Stunnenberg HG, Goldman N, van der Harst P, van der Schoot CE, Ouwehand WH, Albers CA. Nat Genet. 2013 May;45(5):542-5.

The CSB repair factor is overexpressed in cancer cells, increases apoptotic resistance, and promotes tumor growth. Caputo M, Frontini M, Velez-Cruz R, Nicolai S, Prantera G, Proietti-De-Santis L. DNA Repair (Amst). 2013 Apr 1;12(4):293-9.

The CDK subunit CKS2 counteracts CKS1 to control cyclin A/CDK2 activity in maintaining replicative fidelity and neurodevelopment. Frontini M, Kukalev A, Leo E, Ng YM, Cervantes M, Cheng CW, Holic R, Dormann D, Tse E, Pommier Y, Yu V. Dev Cell. 2012 Aug 14;23(2):356-70.

Interaction between the Cockayne syndrome B and p53 proteins: implications for aging. Frontini M, Proietti-De-Santis L. Aging (Albany NY). 2012 Feb;4(2):89-97. Review.

CSA and CSB proteins interact with p53 and regulate its Mdm2-dependent ubiquitination. Latini P, Frontini M, Caputo M, Gregan J, Cipak L, Filippi S, Kumar V, Vélez-Cruz R, Stefanini M, Proietti-De-Santis L. Cell Cycle. 2011 Nov 1;10(21):3719-30.

The ATAC acetyl transferase complex controls mitotic progression by targeting non-histone substrates. Orpinell M, Fournier M, Riss A, Nagy Z, Krebs AR, Frontini M, Tora L. EMBO J. 2010 Jul 21;29(14):2381-94.

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